Female S. mansoni were found to possess an enzyme which could be classified as phenol oxidase. This enzyme was latent and could be activated by in vitro incubation in a tissue culture medium or balanced salt solution. Enzyme activity increased from non-detectable levels up to .41 plus or minus .02 micromoles O2/min/mg protein. The enzyme sedimented in a 1,000 x g pellet and couldn't be solubilized by treatment with detergents, proteolytic and lipolytic enzymes, and freezing and thawing. The enzyme was found to have a pH optimum of 7.0 and was inhibited non-competitively by diethyldithiocarbamate (DDC) and allylthiourea. L-DOPA was the best substrate. L-tyrosine and dopamine were good substrates. Phenol oxidase was localized within the eggshell globules of vitelline cells by fluorescence histochemistry. The fluorescence of the product formed by L-tyrosine methyl ester in this assay was identical to the fluorescence of the product formed from the reaction of phenol oxidase with this substrate in vitro. The concentration of L-tyrosine in the female schistosome (252 ng/mg worm) was 3 times higher than the phenol oxidase Km for L-tyrosine while the concentrations of L-DOPA and dopamine were 100 and 500 times less than the Km for these substrates. Female S. mansoni did not incorporate L-tyrosine preferentially into specific proteins and did not incorporate L-tyrosine into protein to a significantly greater extent than L-leucine. These results suggest that free L-tyrosine is the in vivo substrate for S. mansoni phenol oxidase. Inactive analogs of phenol oxidase inhibitors, peroxidase inhibitors, autooxidation inhibitors and inhibitors of lipid peroxidation were incapable of inhibition formation of the schistosome eggshell at 100 mg/kg in vivo. This dose of a phenol oxidase inhibitor caused 100% inhibition of eggshell formation.